Cerebral blood flow autoregulation has been shown to be affected in a number of important clinical conditions, such as prematurity, birth asphyxia, stroke, head injury, carotid artery disease, hypertension and vasovagal syncope. Acute cerebral diseases (e.g., traumatic brain injury, stroke) frequently lead to a rise in intracranial pressure (ICP) and impairment of cerebral autoregulation (as described in the following references: Aaslid R. et al., Cerebral autoregulation dynamics in humans. Stroke 1989; 20:45-52; Czosnyka M. et al., Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 1997; 41:11-19.; Panerai R. B., Assessment of cerebral pressure autoregulation in humans—a review of measurement methods. Physiol Meas 1998; 19:305-338; and Schondorf R. et al., Dynamic cerebral autoregulation is preserved in neurally mediated syncope. J Appl Physiol 91:2493-2502, 2001).
Assessment of cerebrovascular autoregulation state (CAS) could be of vital importance in ensuring the efficacy of therapeutic measures in the case of brain injury and stroke. Continuous monitoring of CAS and CAS monitoring data based treatment of intensive care patients with brain injuries or stroke will reduce mortality and morbidity of such patients.
Various methods have previously been introduced to assess CAS. Discrete clinical tests (as described in the following references: Aaslid R. et al., Cerebral autoregulation dynamics in humans. Stroke 1989; 20:45-52; and Panerai R. B., Assessment of cerebral pressure autoregulation in humans—a review of measurement methods. Physiol Meas 1998; 19:305-338), like e.g. the cuff leg test (as discussed in reference Aaslid R. et al. Cerebral autoregulation dynamics in humans. Stroke 1989; 20:45-52) did not provide continuous monitoring data about CAS. There is a need for continuous real-time CAS monitoring because is it the optimal monitoring for use with CAS based therapy.
A few methods and techniques (such as those described in the following references: Czosnyka M et al., Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 1997; 41:11-19; and Schmidt B et al., Adaptive noninvasive assessment of intracranial pressure and cerebral autoregulation. Stroke 2003; 43:84-89, 2003) have been proposed for invasive, semi non-invasive and non-invasive monitoring of CAS. These methods are based on the estimation of the correlation factor between arterial blood pressure (ABP) and ICP slow waves or ABP and cerebral blood flow velocity (CBFV) slow waves (as described in the following references: Czosnyka M et al., Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 1997; 41:11-19; and Schmidt B et al., Adaptive noninvasive assessment of intracranial pressure and cerebral autoregulation. Stroke 2003; 43:84-89, 2003). In the case of intact cerebrovascular autoregulation the correlation factor between ABP and ICP slow waves is negative and close to −1.0. In the case of impaired CAS the same factor is positive and close to +1.0.
The disadvantages of slow invasive or non-invasive ABP and ICP wave correlation monitoring methods, include but are not limited to the following.
First, slow ICP waves are not permanent and the amplitude of such waves is too low (less than 3.0 mmHg during main part of ICU patients' continuous monitoring time) in order to measure such waves with sufficient accuracy. Also, non-invasive measurement or prediction of slow ICP waves adds additional errors and distortions of such waves. Further, if invasive slow ICP wave measurement is replaced by non-invasive transcranial Doppler (TCD) CBFV measurement, additional errors and distortions of such waves will occur. Moreover, slow ABP waves are also too small to measure with sufficient accuracy and non-invasively.
Also, the period of slow ICP or ABP waves is estimated to be from approximately 30 seconds to 120 seconds or more. In order to evaluate the CAS applying the slow wave method, it is necessary to accumulate the measured data during 4.0 minutes or longer. This is a relatively long time period and thus becomes a long term process. Long time period testing of CAS is not always effective because variability of CAS is a short-term process (as described in the following reference: Panerai R B et al., Short-term variability of cerebral blood flow velocity responses to arterial blood pressure transients. Ultrasound in Med. & Biol., Vol. 29, No. 1, pp. 31-38, 2003). Because the time delay of CAS monitoring data, secondary brain insults and injury can take place in ICU coma patients before appearance of the CAS monitoring data. The time delay of the slow wave CAS monitoring method is therefore too long for clinical practice of ICU patients monitoring and CAS based treatment.
Additionally, cerebrovascular autoregulation is complex, nonlinear and a multivariate mechanism with considerable short-term variability (as described in the following reference: Panerai R. B. et al., Short-term variability of cerebral blood flow velocity responses to arterial blood pressure transients. Ultrasound in Med. & Biol., Vol. 29, No. 1, pp. 31-38, 2003). A correlation factor can be applied without problems as an indicator of CAS only in linear autoregulatory systems. However, cerebrovascular autoregulation system is nonlinear (as described in the following reference: Panerai R. B. et al., Linear and nonlinear analysis of human dynamic cerebral autoregulation. Am J Physiol 1999a; 277:H1089-H1099). Any correlation factor between a reference signal (ABP slow wave) and a nonlinearly distorted cerebrovascular autoregulation system output signal (ICP or CBFV slow wave) would be a questionable indicator of CAS.
Accordingly, it is an object of the present invention to provide a method and apparatus for continuous real-time CAS monitoring that solves the problems and cures the deficiencies of the prior art methods, apparatuses and techniques.
The present invention provides a method for continuous real-time CAS monitoring which is based on simultaneous, non-invasive monitoring of intracranial blood volume respiratory waves (or other intracraniospinal characteristics related to the respiration processes) and lung volume respiratory waves (or other extracranial physiological characteristics related to the lung respiration processes), real-time decomposition or filtering of intracranial blood volume respiratory waves and lung volume respiratory waves into narrowband sinewave first harmonic components, determination therefrom of the phase shift between intracranial blood volume respiratory wave and lung volume respiratory wave first harmonics' and derivation of cerebrovascular autoregulation state from that phase shift value.
The intracranial blood volume (IBV) and lung volume (LV) respiratory waves have much shorter period (typically 2.5 seconds to 10.0 seconds) than slow waves. Respiratory waves are permanent in all conditions of ICU patients. Lung respiratory waves, as a reference signal for CAS estimation, can be measured non-invasively with accuracy much higher than non-invasive ABP slow wave measurements. Also IBV respiratory waves can be measured non-invasively with much higher accuracy than ICP or IBV slow wave measurements (as described in the following reference: Ragauskas et al., Implementation of non-invasive brain physiological monitoring concepts. Medical Engineering & Physics 25(2003) 667-678). It is not necessary to accumulate more than one period of non-invasively recorded IBV and LV respiratory wave data in order to estimate CAS. Because of that, the present invention provides a method of CAS monitoring which is much closer to a real-time method when compared with the slow wave method.